title: Near-infrared-excited confocal Raman spectroscopy advances in vivo diagnosis of cervical precancer.
abstract: Raman spectroscopy is a unique optical technique that can probe the changes of vibrational modes of biomolecules associated with tissue premalignant transformation. This study evaluates the clinical utility of confocal Raman spectroscopy over near-infrared (NIR) autofluorescence (AF) spectroscopy and composite NIR AF/Raman spectroscopy for improving early diagnosis of cervical precancer in vivo at colposcopy. A rapid NIR Raman system coupled with a ball-lens fiber-optic confocal Raman probe was utilized for in vivo NIR AF/Raman spectral measurements of the cervix. A total of 1240 in vivo Raman spectra [normal (n=993), dysplasia (n=247)] were acquired from 84 cervical patients. Principal components analysis (PCA) and linear discriminant analysis (LDA) together with a leave-one-patient-out, cross-validation method were used to extract the diagnostic information associated with distinctive spectroscopic modalities. The diagnostic ability of confocal Raman spectroscopy was evaluated using the PCA-LDA model developed from the significant principal components (PCs) [i.e., PC4, 0.0023%; PC5, 0.00095%; PC8, 0.00022%, (p<0.05)], representing the primary tissue Raman features (e.g., 854, 937, 1095, 1253, 1311, 1445, and 1654 cm(-1)). Confocal Raman spectroscopy coupled with PCA-LDA modeling yielded the diagnostic accuracy of 84.1% (a sensitivity of 81.0% and a specificity of 87.1%) for in vivo discrimination of dysplastic cervix. The receiver operating characteristic curves further confirmed that the best classification was achieved using confocal Raman spectroscopy compared to the composite NIR AF/Raman spectroscopy or NIR AF spectroscopy alone. This study illustrates that confocal Raman spectroscopy has great potential to improve early diagnosis of cervical precancer in vivo during clinical colposcopy.
authors.affiliation: National University of Singapore, Department of Bioengineering, Faculty of Engineering, Optical Bioimaging Laboratory, Singapore.
authors.forename: Shiyamala
authors.initials: S
authors.lastname: Duraipandian
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Joseph
authors.initials: J
authors.lastname: Ng
authors.forename: Jeffrey J H
authors.initials: JJ
authors.lastname: Low
authors.forename: Arunachalam
authors.initials: A
authors.lastname: Ilancheran
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D002471:Cell Transformation, Neoplastic; D005260:Female; D005336:Fiber Optic Technology; D006801:Humans; D018613:Microscopy, Confocal; D008875:Middle Aged; D015999:Multivariate Analysis; D011166:Porphyrins / Q000737:chemistry; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000473:pathology; D025341:Principal Component Analysis; D012372:ROC Curve; D013053:Spectrophotometry; D019265:Spectroscopy, Near-Infrared; D013059:Spectrum Analysis, Raman; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000473:pathology; D055815:Young Adult
chemical_list: D011166:Porphyrins